JNK激酶抑制剂SP600125对大鼠皮瓣缺血再灌注损伤的保护作用  

Protective effect of JNK inhibitor SP600125 on rat skin flap ischemia/reperfusion injury

作　　者：刘艺芳[1] 张明子[2] 王友彬[2] 马雪梅[1] 

机构地区：[1]北京工业大学生命科学与生物工程学院,北京100124 [2]北京协和医院整形外科,北京100730

出　　处：《世界临床药物》2016年第9期599-603,共5页World Clinical Drug

基　　金：北京市自然科学基金项目(编号:7132169)

摘　　要：目的探讨SP600125对SD大鼠腹部皮瓣缺血再灌注损伤的保护作用及其机制。方法雄性SD大鼠36只随机分为3组,假手术组(SH组),缺血再灌注/注射SP600125组(I/R-SP组)和缺血再灌注/注射DMSO溶液组(I/R-D组),每组12只,后两组大鼠通过夹闭左腹腹壁下浅动脉3 h后恢复血流供给制备腹部皮瓣缺血再灌注模型。血流恢复24 h,每组随机挑选6只大鼠进行免疫组化检测,比较p JNK、Bcl-2和Bax蛋白的表达水平;血流恢复72 h,采用激光多普勒血流灌注成像仪检测各组剩余(6只)大鼠皮瓣的血流灌注情况,并通过HE染色和TUNEL染色观察组织学变化和细胞的早期凋亡。结果免疫组化结果显示,与I/R-D组相比,I/R-SP组p JNK,Bax蛋白表达水平显著降低,Bcl-2表达水平显著增高;皮瓣血流灌注情况显示,I/R-SP组成活率及血流灌注量均显著高于I/R-D组,差异有统计学意义(P<0.01);皮瓣组织细胞凋亡率,I/R-SP组显著低于I/R-D组(P<0.01)。结论 SP600125可能通过抑制JNK通路,减少细胞凋亡,从而缓解皮瓣缺血再灌注损伤。Objective To investigate the protective effect of JNK inhibitor SP600125 on the rat skin flap ischemia/reperfusion injury and its possible mechanism.Methods Thirty six Sprague-Dawley rats were divided into sham surgery group（SH group） and two surgery groups（I/R-SP group with SP600125 and I/R-D group with DMSO）,12 rats in each group.The abdominal flap ischemia reperfusion model was made by clamping the left abdominal wall of rat＇s lower superficial artery for 3 h and then to recovery blood supply.After 24 h of skin flap perfusion,6 rats were randomly selected from each group,their pJNK,Bcl-2 and Bax were examined by immunohistochemistry.After 72 h of skin flap perfusion,the remaining 6 rats in each group were selected,their blood perfusion of flap were measured by Laser Doppler flow meter,HE staining was used to observe morphological changes,early apoptosis was observed through TUNEL staining.Results The immunohistochemical staining showed that the levels of pJNK and Bax in I/R-SP group were lower than those in I/R-D group,and the level of Bcl-2 was higher.Compared with the I/R-D group,the flap survival rate and flap perfusion in I/R-SP group were significantly increased（P〈0.01）,the percentage of apoptotic cells in I/R-SP group was significantly decreased（P〈0.01）.Conclusion SP600125 can relieve the ischemia/reperfusion injury of the skin flap.Its mechanism may be to inhibit the JNK pathway and reduce the apoptosis of the cells.

关 键 词：皮瓣 缺血再灌注损伤 SP600125 

分 类 号：R982[医药卫生—药品]